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Title: Blueprint Virology
Description: This document contains elaborate study materials of the Virology course for both Bachelor and Masters level. It covers both General and Systemic Virology. Total page number: 80. There are questions and answers included in various topics like "Cultivation of viruses; Viral genetics and replication; Oncogenic viruses; Hepatitis viruses; Herpes viruses; Non-oncogenic retroviruses; Slow viral infections" and so on.
Description: This document contains elaborate study materials of the Virology course for both Bachelor and Masters level. It covers both General and Systemic Virology. Total page number: 80. There are questions and answers included in various topics like "Cultivation of viruses; Viral genetics and replication; Oncogenic viruses; Hepatitis viruses; Herpes viruses; Non-oncogenic retroviruses; Slow viral infections" and so on.
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Virology
Reference Books
1
...
)
Wiley-Blackwell Publication
2
...
)
Wiley-Blackwell Publication
3
...
)
Wiley-Blackwell Publication
4
...
)
ASM Press
5
...
)
By Nicholas H
...
Introduction to Modern Virology (6th Ed
...
Define virus
...
Virus: Viruses are non-cellular particles composed of an internal core containing either DNA or RNA (but not
both) covered by a protective protein coat and they are not capable of independent replication, can synthesize
neither their own energy nor their proteins and are too small to be seen in the light microscope
...
2
...
4
...
6
...
8
...
10
...
12
...
Viruses are the smallest infectious agents (size: 20-300 nm in diameter)
...
Viruses are obligate intracellular parasites
...
Viruses multiply by a process known as replication
...
Parasite at genomic level
...
Viruses do not have a nucleus, cytoplasm, mitochondria or ribosome
...
Cannot synthesize protein due to absence of ribosome
...
They grow only in cell culture media
...
Viruses are sensitive to interferon
...
Viruses can act as a genomic vector
...
So they cannot generate
energy or synthesize protein due to absence of enzyme
...
Because they can reproduce only within cells, viruses are obligate
intracellular parasites
...
They cannot synthesize sufficient energy to replicate independently
...
What are the differences between viruses and bacteria?
Differences between viruses and bacteria:
1
...
Traits
Cells
Size
No
20-300 nm
3
...
5
...
7
...
Motility
9
...
Multiplication
11
...
Metabolic activity
13
...
Interferon sensitivity
Virus
Either DNA or RNA, never both
None
Absent
Protein capsid and lipoprotein
envelope
None
Not seen by light microscope
Replication or lysogeny
Cannot be cultured in artificial and
cell-free media
...
g
...
Usually extracellular, some are
intracellular
...
Some
Usually seen by light microscope
Binary fission
Can be cultured in artificial and cell-free
media
...
Give the structure of a complete virus particle
...
Some viruses have envelope outside the capsid
...
These DNA and RNA genomes can be either single stranded or double stranded or linear or circular
...
All viruses are haploid except retroviruses, which are diploid
...
Functions of capsid proteins:
1
...
3
...
Protect the nucleic acid from the host nuclease
...
Act as antigens that induce antibody formation and active cytotoxic T cells to kill virus-infected cells
...
Envelope:
•
•
The viral envelope consists of a membrane that contains lipid derived from the host cell and proteins
encoded by the virus
...
Enveloped viruses are less stable then naked viruses
...
2
...
Q
...
Viruses that have an
icosahedral nucleocapsid can be either enveloped or naked
...
All human viruses that have a helical nucleocapsid, are enclosed by an outer membrane called an envelope,
i
...
, there are no naked helical viruses
...
What do you mean by atypical virus like agents?
Atypical virus like agents: There are four exceptions to a typical virus:
1
...
3
...
Defective
Pseudovirions
Viroids
Prions
Q
...
In general, the presence of an envelope confers instability on the virus
...
Non-enveloped viruses are composed of only of nucleic acid and capsid proteins
...
Q
...
The virion is either a naked or
an enveloped nucleocapsid
...
In case of herpes virus, it may be the
whole one
...
What do you mean by pseudovirions?
Pseudovirions: Pseudovirions contain host cell DNA instead of viral DNA within the capsid
...
Pseudovirions can infect cells, but they do not replicate
...
Write short note on: Defective virus
...
Example: Hepatitis D virus is a defective virus as it cannot replicate without the presence of hepatitis B virus
...
Significance/Importance:
1
...
During the growth of most human viruses, many more defective than infectious are produced
...
Because the defective particles can interfere with the growth of the infectious particles, they can aid in
recovery from an infection by limiting the ability of the infectious particles to grow
...
What do you mean by viroids?
Viroids: Viroids consist solely of a single molecule of circular RNA without a protein coat or envelope
...
Nevertheless, viroids replicate but the
mechanism is unclear
...
Q
...
Definition
2
...
Protein coat
4
...
Size
6
...
Either DNA or RNA
Present
May be present
Larger
Infects all types of organisms
...
Only RNA
Absent
Absent
Smaller
Infects only plants
...
Write short note on: Prion
...
They have no DNA or RNA
...
2
...
Mad cow disease and scarpie in animals
...
2
...
4
...
Prions are much more resistant to inactivation by ultraviolet light and heat than are viruses
...
Prion proteins are encoded by a cellular gene
...
Q
...
Differences between prion and virus:
Feature
1
...
Particle contains protein
3
...
Appearance in electron microscope
Prions
No
Yes, encoded by cellular genes
...
5
...
Infection includes inflammation
No
No
6
Virus
Yes
Yes, encoded by viral genes
...
Yes
Yes
Classification of Virus
Q
...
Classification of viruses: According to the suggestion of ICVN (International Committee on Nomenclature of
Viruses), classification counts the following basis:
1
...
3
...
5
...
Type of nucleic acid
Strandedness (whether nucleic acid is single stranded or double stranded)
Presence of envelope
Character of nucleic acid: Positive or negative strand
Symmetry of genome
Ether sensitivity
1
...
On the basis of strandedness:
Double stranded viruses
• Hepatitis B virus
• Herpes simplex virus
• Small pox virus
• Rota virus
• Adenovirus
All DNA viruses except parvo virus
...
On the basis of presence of envelope:
Enveloped viruses
• Hepatitis B virus
• Herpes simplex virus
• Small pox virus
4
...
On the basis of symmetry of genome:
Icosahedral virus
• Hepatitis B virus
• Herpes simplex virus
• Adenovirus
Single stranded viruses
• Hepatitis A virus
• Polio virus
• Dengue virus
• Measles virus
• Influenza virus
All RNA viruses except reovirus
...
On the basis of ether sensitivity:
Ether sensitive
• Herpes simplex virus
• Myxovirus
• Corona virus
All enveloped viruses except pox
virus
...
All RNA viruses are single stranded except Reovirus
...
Q
...
All of these viruses (there are over 350 of them) have a complex cycle involving arthropods as vectors
that transmit the viruses to vertebrate hosts by their bite
...
Human pathogens include dengue, yellow fever, encephalitis viruses and
others
...
Q
...
The term ‘retro’ pertains to the reverse transcription of the RNA genome into DNA
...
2
...
Oncovirus group, which contains the sarcoma and leukemia viruses, e
...
, human T cell leukemia virus
(HTLV)
...
g
...
A third group is spumaviruses (non-pathogenic to human)
...
2
...
Hosts remain chronically infected
...
Mention the steps of virus replication
...
Attachment or adsorption: First of all, a virus binds with a specific receptor on host cell surface
...
For example, HIV binds with CD4 receptor
to T cell
...
Entry or penetration: After binding, the virus particle is taken up inside the cell
...
This occurs by• Receptor mediated endocytosis
...
• Fusion of the virus envelope with the cell membrane
...
Ucoating: Uncoating is the physical separation of the viral nucleic acid from the outer structural
components of the virion so that it can function
...
Early transcription: Synthesis of early viral mRNA from the viral nucleic acid (NA)
...
Early translation: synthesis of early viral protein/non-structural protein/enzyme from mRNA
...
Viral genome replication
...
Late transcription: Synthesis of late viral mRNA from the viral nucleic acid
...
Late translation: Synthesis of late viral protein/structural protein/capsid protein
...
Condensation: Accumulation of nucleic acid and capsid protein in the nucleus or cytoplasm
...
Assembly: Packaging of the viral nucleic acid within the capsid proteins forms the progeny viruses
...
Release of progeny viruses: It occurs either of two processes:
• In case non-enveloped viruses, there is rupture of the cell membrane and release of the mature
particles
...
During this budding process, these viruses acquire their envelope
...
The poxviruses are the exception because they replicate in the
cytoplasm
...
The two principal exceptions
are retroviruses and influenza viruses, both of which have an important replicative step in the nucleus
...
What do you mean by eclipse period and latent period?
Eclipse period: Sometime after replication, the virus disappears but the viral nucleic acid continues to function and
begins to accumulate within the cell
...
The eclipse period ends with the appearance of virus
...
Latent period: The latent period is defined as the time from the onset of infection to the appearance of virus
extracellularly
...
Nice to know:
Positive polarity RNA genome: If viral genome RNA is identical to its mRNA, then it is said to be positive polarity
RNA genome
...
Transcription: Synthesis of one type of nucleic acid on the basis of base sequence of DNA or RNA
...
Early proteins: The viral proteins which are synthesized before the replication of the viral genome are known as
early proteins
...
They are absent in the virion
structure
...
Late proteins: The viral proteins which are synthesized after the replication of the viral genome are called late
proteins
...
They are present in the virion structure
...
Q
...
Lysogeny: Lysogeny or lysogenic cycle is the process by which viral DNA becomes integrated into host cell DNA,
replication stops and no progeny virus is made
...
Later, if DNA is damaged by, for example, UV light, viral DNA is excised from the host cell
DNA and progeny viruses are made
...
Q
...
Lysogenic conversion: Lysogenic conversion is the term applied to the new properties that a bacterium acquires
as a result of expression of the integrated prophage genes
...
Toxins produced by lysogenic bacteria:
•
•
•
•
Diphtheria
Botulinum
Cholera
Erythrogenic toxins
Mechanism of lysogenic conversion: It is mediated by the transduction of bacterial genes from the donor bacterium
to the recipient bacterium by bacteriophages
...
Q
...
Types of phages: According to the replication cycle, phages are of two types:
1
...
Virulent phage (Lytic phage): The lytic phages infect bacterial cells, multiply there and then cause rupture
of the bacterial cell membrane and then released from that cell
...
Temperate phage: The temperate phages infect bacterial cells and then viral genome is integrated with
host DNA and no progeny virus particles are produced at that time
...
Importance:
1
...
Lysogenic conversion: Temperate phages add their genome to the host bacterial genome and make them
toxigenic
...
Temperate phages are not suitable for phage therapy, as they are very virulent
...
Write down the steps of viral pathogenesis
...
2
...
4
...
6
...
Transmission and entry of the virus into the host
...
Tropism
...
Cell injury and clinical illness
...
Virus shedding
...
How does viruses are transmitted?
Transmission of virus and their entry: Viruses are transmitted via two routes:
1
...
Horizontal route (person to person transmission): Virus enters the host through a variety of routes,
including direct transmission, respiratory, conjunctiva, GIT, genitourinary routes, break in the skin or
mucosal surfaces
...
Spread in the host: Viruses produce either localized or disseminated infection
...
2
...
Disseminated infection: Viruses spread and cause systemic infection by two major routes:
a
...
b
...
Nice to know:
Tropism: Tropism is the capacity of viruses to infect a specific type of cell type within a tissue or organ
...
Virulence and cytopathogenicity: The ability of a virus to cause disease in an infected host is called virulence or
pathogenicity
...
Cell injury and clinical illness:
•
•
The symptoms of viral disease are usually caused by death of the infected cells and a consequent loss of
function
...
Immunopathogenesis is the process by which the symptoms of viral diseases are caused by the immune
system rather than the killing of cells directly by the virus
...
Damage to the
liver caused by hepatitis viruses occurs by this mechanism
...
Arthritis associated with
parvovirus B 19 or rubella virus infection occurs by this mechanism
...
Recovery mechanisms include
both innate and adaptive immune responses
...
Virus shedding: The last stage in pathogenesis is the shedding of infectious virus into the environment
...
Shedding usually occurs from the body surfaces
11
involved in viral entry
...
Q
...
Tissue and cell tropism by a given virus usually reflect the presence of specific cell surface receptors for that
virus
...
2
...
For example:
• Hepatitis virus: Hepatocyte
• Influenza virus: Upper respiratory tract epithelium
...
Q
...
Inclusion body: Inclusion bodies are virus specific intracellular globular masses produced during replication of
virus
...
Owl’s eye inclusions in the nucleus of cytomegalovirus infected cells
...
2
...
Intracytoplasmic inclusion bodies: Formed in the cytoplasm, e
...
• Guarnieri’s bodies in small pox and vaccinia virus infection
...
g
...
g
...
• Cow dry type B- (Compact and may be multiple) e
...
, Poliomyelitis
...
g
...
Importance: They are visible under light microscope and therefore are important tools to diagnose a viral infection
...
What are the changes that occur in virus infected cell?
Effects of virus infection on cell:
1
...
3
...
5
...
g
...
Formation of multinucleated giant cells: By fusion of virus-infected cells, e
...
, after infection with
herpesviruses and paramyxoviruses
...
No apparent morphologic or functional change
...
12
6
...
Changing antigenic surface to host cell
...
Q
...
Features of cytopathic
effects are morphologic changes of the cell organelles followed by cellular lysis
...
Cytoplasm: Inclusion bodies, vacuoles
...
Cellular: Lysis (disintegration)
...
2
...
CPE is the basis for the plaque assay, an important method for quantifying the amount of virus in a sample
...
What do you mean by• Chronic carrier infection
• Latent infection
• Slow virus infection
Chronic carrier infection: Carrier state refers to people who produce virus for long periods of time and can serve
as a source of infection for others
...
Examples of chronic carrier infection: Chronic hepatitis B and C, neonatal rubella virus and cytomegalovirus
infections
...
Examples of latent infection:
Virus
Herpes simplex virus 1
Herpes simplex virus 2
Varicella Zoster virus
Epstein Barr virus
Cytomegalovirus
Initial infection
Eyes and face
Genital organs
Varicella (chickenpox)
Site of Latent infection
Cranial sensory ganglia (trigeminal ganglia)
Lumber and sacral sensory ganglia
Trigeminal or thoracic ganglia
B lymphocyte
Leukocytes, kidney, glands
...
Example:
•
Slow virus infection caused by viruses:
Subacute sclerosing panencephalitis follows several years after measles virus infection
...
• Slow virus infections caused by prions:
1
...
2
...
2
...
Innate (Non-specific):
1
...
2
...
3
...
4
...
B
...
Active immunity:
a
...
b
...
2
...
3
...
Q
...
Herd immunity: Herd immunity, also known as community immunity, population immunity or social immunity
is the protection of an individual from infection by virtue of the other members of the population (the herd) being
incapable of transmitting the virus to that individual
...
1
...
2
...
Live attenuated polio vaccine provides herd immunity becausei
...
ii
...
Q
...
Basis of viral oncogenesis:
1
...
3
...
5
...
Evasion of host immune responses: Viruses that establish persistent infections must avoid detection and
recognition by the immune system that would eliminate the infection
...
This occurs by• Direct acting: The tumor viruses introduces a new transformating gene into the cell
...
Cell susceptibility to viral infections: Not all cells from the natural host species are susceptible to viral
replication or transformation or both
...
Retention of tumor virus nucleic acid in a host cell: This is accomplished by the integration of certain
viral genes into the host cell genome
...
What is viral interference?
Or Write short note on: Viral interference
...
This is called viral interference
...
2
...
Live attenuated polio vaccine interferes with the infection with wild virus
...
Pre-existent wild viruses may interfere the super infection by live attenuated virus
...
State the methods of laboratory diagnosis of viral diseases
...
2
...
4
...
Identification of the virus in cell culture
...
Serologic procedures to detect a rise in antibody titer or the presence of IgM antibody
...
Detection of viral nucleic acids in blood or the patients’ cells
...
2
...
4
...
6
...
Blood
Sputum
Nasal swab
Throat washings
Stool, urine, CSF
Biopsy
Autopsy materials
Identification in cell culture: Viruses can be cultured in cell culture media and detected by seeing cytopathic effect
(CPE)
...
e
...
Microscopic identification: Viruses can be detected and identified by direct microscopic examination of clinical
specimens by three procedures:
1
...
3
...
UV microscopy: Used for fluorescent antibody staining of the virus in infected cells
...
Serological techniques or Detection of antibodies:
•
•
•
•
•
A rise in the titer of antibody to the virus can be used to diagnose current infection
...
Presence of IgG indicates either current infection or past infection or vaccination
...
Antibody titer can be determined by CIE, RIA, ELISA immunodiffusion test
...
For example, p24 of HIV and hepatitis B surface antigen are
commonly used in diagnosis
...
Labeled probes are highly specific and results are rapidly obtained
...
Q
...
Viral culture media: Cell cultures are of 3 types:
1
...
g
...
16
2
...
Semi continuous diploid cells: These are derived from human fetal tissues and can be subcultured 20 to
50 times e
...
, human diploid fibroblasts such as MRC-5
...
g
...
Q
...
Viruses cannot be cultured in ordinary media; cell is needed
...
Why antiviral drugs are so rare?
Difficulties in developing antiviral drugs:
1
...
3
...
As the viruses use normal host cell machinery to synthesize their own structural protein and enzyme,
achieving selective toxicity is very difficult
...
By the time the patient becomes symptomatic, the
virus has already spread and then it becomes difficult to stop the replication of virus
...
g
...
Some viruses have the capability to undergo rapid and many mutations and these mutant viruses become
resistant to antiviral drugs
...
Classify antiviral drugs according to mechanism of action
...
Early event inhibitors
1
...
Viral uncoating inhibitors
Antiviral drugs
Enfuviride
• Amantadine
• Rimantadine
B
...
Inhibitors of hepatitis viruses (HSV)
• Nucleoside viral DNA polymerase inhibitors
• Non-nucleoside viral DNA polymerase inhibitors
2
...
Inhibitors of other viruses
C
...
Viral protein synthesis inhibitors
18
•
•
•
•
•
•
•
•
•
Acyclovir
Ganciclovir
Famciclovir
Valacyclovir
Cidofovir
Vidarabine
Iododeoxyuridine
Trifluorothymidine
Foscarnet
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Azidothymidine
Dideoxyinosine
Dideoxycytidine
Lamivudine
Stavudine
Abacavir
Tenofovir
Nevirapine
Delavirdine
Efavirenz
Ribavirin
Adefovir
Saquinavir
Nelfinavir
Indinavir
Amperenavir
Ritonavir
Atazanavir
Interferon
Fomivirsen
•
•
•
E
...
A vaccine typically
contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms
of the microbe, its toxins or one of its surface proteins
...
Because few drugs are useful against viral infections, prevention of infection by the use of vaccine is very important
...
Q
...
Common viral vaccines:
Type of vaccine
Live
Live and killed
Killed
Subunit
•
•
•
•
•
•
•
•
•
•
•
•
Vaccine
Measles
Mumps
Rubella
Varicella (chickenpox)
Zoster
Rota virus
Polio
Influenza A and B
Rabies
Hepatitis A
Hepatitis B (HBsAg)
Papilloma (LI)
Viral vaccine used in special situations:
Live
• Yellow fever1
• Adenovirus
• Small pox2
Japanese encephalitis
Killed
1
Used when travelling in endemic areas
...
Q
...
Killed virus vaccine: An inactivated or killed vaccine consists of virus particles which are grown in culture and
then killed using a method such as heat or formaldehyde
...
Advantages:
1
...
3
...
Stability at room temperature is high
...
20
Disadvantages:
1
...
3
...
5
...
7
...
Duration of immunity is shorter
...
Less effective than live vaccine
...
Cell mediated response to inactivated vaccine is generally poor
...
Some killed virus vaccines have induced hypersensitivity to subsequent infection
...
Q
...
As a result, gut immunity does not develop after vaccination with
injectable killed vaccine
...
State the advantages and disadvantages of live viral vaccine
...
That is, their antigenicity is preserved but pathogenicity is lost
...
2
...
4
...
6
...
8
...
Boosters are required less frequently
...
Adequate cell mediated immunity is produced
...
May give herd immunity
...
Quick immunity
...
g
...
Disadvantages:
1
...
3
...
Reversion to virulence: Inactivated virus may regain pathogenicity and cause disease
...
Can be difficult to transport due to requirement to maintain conditions e
...
, temperature
...
Q
...
Disadvantages of viral vaccines:
1
...
3
...
g
...
This can cause anaphylactic reaction
...
Viral vaccine may be ineffective due to antigenic change in virus (antigenic shift and drift)
...
Compare the characteristics of killed and live viral vaccine
...
2
...
4
...
6
...
8
...
10
...
12
...
Characteristics
Number of doses
Need for adjuvant
Duration of immunity
Effectiveness of protection (more closely mimics natural infection)
Immunoglobulins produced
Mucosal immunity produced
Cell mediated immunity produced
Residual virulent virus in vaccine
Reversion to virulence
Excretion of vaccine virus and transmission of non-immune contacts
Interference by other viruses in host
Stability at room temperature
Interruption of transmission of virulent virus
22
Killed vaccine
Multiple
Yes
Shorter
Lower
IgG
Poor
Poor
Possible
No
No
No
High
Less effective
Live vaccine
Single
No
Longer
Greater
IgA and IgG
Strong
Strong
No
Possible
Possible
Possible
Low
More effective
Herpesviruses
Q
...
Herpes virus: The herpesviruses that commonly infect humans include:
1
...
3
...
5
...
7
...
Herpes simplex virus type 1 (HSV -1)
Herpes simplex virus type 2 (HSV-2)
Varicella zoster virus (VZV)
Cytomegalovirus (CMV)
Epstein Barr virus (EBV)
Human herpes virus 6 (HHV 6)
Human herpes virus 7 (HHV 7)
Human herpes virus 8 (HHV 8)/Kaposi sarcoma associated herpesvirus (KSHV)
Q
...
Characteristics of herpes viruses:
1
...
3
...
5
...
Shape: Spherical
...
Capsid: Icosahedral
...
Replication: They replicate in the nucleus and form intra-nuclear inclusions
...
Encode many enzymes
...
No viral polymerase enzymes are produced
...
c
...
d
...
e
...
f
...
g
...
Nice to know:
Herpes
virus
HSV-1
HSV-2
VZV
Primary infection
Gingivostomatitis
Herpes
perinatal
disease
Varicella
genitalis,
disseminated
EBV
Infectious
mononucleosis
CMV
Congenital infection (in
utero), mononucleosis
Usual site of
latency
Cranial
sensory
ganglia
Lumber or sacral
ganglia
Recurrent
infection
Herpes labialis,
encephalitis,
keratitis
...
Via respiratory secretions and
saliva – during kissing (teenager
and young adults)
1
...
2
...
Adults:
Sexually
transmission
...
Others:
Blood
transfusion,
organ
transplantation
...
Q
...
1
...
Herpes simplex virus type-2 (HSV-2)
3
...
Cytomegalovirus (CMV)
5
...
Human herpes virus 6
7
...
Human herpes virus 8
Diseases
Gingivo-stomatitis
Recurrent herpes labialis
Keratoconjunctivitis
Encephalitis
Genital ulcer
Finger infections (whitlows)
Eczema herpeticum
Genital herpes
Neonatal herpes
Cervical and vulvar carcinoma
Encephalitis, acute meningitis or transverse
myelitis
...
• Zoster (Shingles) – recurrent form in adults
...
• Infectious
mononucleosis
(heterophile
antibody-negative)
• Hepatitis
• Disease in immunocompromised patients:
retinitis, encephalitis, pneumonitis, hepatitis,
enteritis
...
Latest, non-pathogenic and may be helpful against
HIV
...
•
•
•
•
•
•
•
•
•
•
•
Q
...
In these sites of latent infection, immune
system cannot attack and destroy them
...
Q
...
Herpes viruses associated with malignancy:
Herpes viruses
Malignancy
1
...
2
...
Human herpes virus 8
•
•
•
•
Burkit’s lymphoma
Nasopharyngeal carcinoma
Other lymphomas
Kaposi’s sarcoma
24
•
Primary effusion lymphoma
...
2
...
Usually by infected saliva
...
Respiratory droplets
...
1
...
3
...
5
...
7
...
9
...
Herpes labialis: Herpes labialis (fever blisters or cold sores) is characterized by crops of vesicles, usually
at the mucocutaneous unction of the lips or nose
...
Recurrent keratoconjunctivitis: Recurrences can lead to corneal ulcers, scarring and blindness
...
It can occur medical personnel as a
result of contact with patient’s lesions
...
It is characterized by
vesicular lesions on the head, neck and trunk
...
Pharyngitis and tonsillitis
...
Latent infections: The virus becomes latent in the sensory ganglion cells
...
Factors which reactivates HSV-1 from the latent stage: The virus can be reactivated from latent state by a variety
of inducers, e
...
,
1
...
3
...
5
...
Sunlight
Hormonal changes
Trauma
Stress
Fever
Axonal injury
After reactivation, it migrates down the neuron and replicates in the skin, causing lesions
...
Describe the pathogenesis of herpes labialis
...
↓
From primary site of replication, the virus enters the local nerve endings and is transported by retrograde axonal
flow to trigeminal ganglia
...
↓
25
After reactivation of the viruses, they pass down the axon to the primary site of infection where they produce
vesicles at the mucocutaneous junction
...
How will diagnose HSV-1 in the laboratory?
Laboratory diagnosis of HSV-1:
1
...
3
...
Isolation and identification of virus by cell culture
...
The presence of multinucleated giant cells suggests
herpesvirus infection
...
Serologic tests such as the neutralization test can be used in the diagnosis of primary infections
...
For HSV-1 eye infections, trifluridine is used topically
...
Herpes simplex virus type – 2 (HSC – 2)
Diseases:
1
...
3
...
Genital herpes: Painful vesicular lesions of the male and female genitals and anal area
...
Neonatal herpes varies from severe diseases (e
...
, disseminated lesions or encephalitis) to milder
local lesions (skin, eye, mouth) to asymptomatic infection
...
Erythema multiforme
...
How can you prevent neonatal herpes?
Neonatal diseases may be prevented by performing cesarean section on women with either active lesions or positive
viral cultures
...
2
...
The neonate/fetus may be infected from the birth canal of the mother during labor
...
↓
Virus then invades the local nerve ending and transported by retrograde axonal flow to the lumber and sacral dorsal
root ganglion where they develop latency
...
The activating factors are same as HSV-1
...
Lab diagnosis:
1
...
3
...
But in recurrent infection,
usually there is no four-fold rise of IgG into serum samples
...
Isolation and identification of virus by cell culture
...
PCR: PCR is the most sensitive test for HSV diagnosis
...
Prevention:
1
...
Cesarean section is recommended for women who are at term and who have genital lesions or positive
viral cultures
...
Q
...
They can however, be
differentiated by the restriction endonuclease patterns of the genome DNA and by type-specific
monoclonal antisera
...
Lesions caused by HSV-1 are, in general, above the waist, whereas those caused by HSV-2 are below the
waist
...
Mouth
Eye
Central nervous system
Neonate
Gingivostomatitis
Keratoconjunctivitis
Encephalitis
Rare1
Dissemination to viscera and Yes
immunocompromised patients
1
Infection acquire after birth from HSV-1 – infected person
...
Rare
Rare
Rare
Skin
lesions,
encephalitis
disseminated infection2
Rare
waist
and
Infection acquired during passage through birth canal
...
Q
...
Q
...
↓
Initial replication in the regional lymph nodes
...
↓
27
Swelling of epithelial cells, ballooning degeneration and the accumulation of tissue fluid result in vesicle formation
...
What is the reactivation lesion of chicken pox and how it occurs?
Reactivation lesion of chicken pox is Zoster
...
↓
Later in life, frequently at times of reduced cell-mediated immunity or local trauma, the virus is activated and passes
down from dorsal root ganglia and causes the vesicular skin lesions and nerve pain of Zoster
...
Zoster usually occurs only once
...
Complication of chicken pox:
1
...
3
...
2
...
4
...
Diagnosis is usually clinical
...
Microscopic examination of scrapings or swabs of the base of vesicles
...
Rapid diagnostic procedures are:
• Detection of antigen (direct immunofluorescence)
• Detection of viral DNA by PCR
...
Serology: A rise in antibody titer can be used to diagnose varicella but is less useful in the diagnosis of
zoster, since antibody is already present
...
Treatment:
•
•
•
Immunocompetent children with chicken pox or zoster → No antiviral therapy
...
Immunocompromised children and adults with chickenpox, zoster or disseminated disease → Acyclovir
...
There are two vaccines against VZV
...
2
...
Zostavax: It prevents zoster and is recommended for people older than 60 years and who have had
varicella
...
A young man had a history of short prodromal period followed by low grade fever for few days, then painful
ulcer on the lips and neck without medication
...
What will be the agent responsible for it?
Viral agent is responsible
...
28
Cytomegalovirus
Cytomegalovirus is the most common intrauterine infection associated with congenital defects
...
What are the routes of transmission and complications of Cytomegalovirus?
Diseases or complications of Cytomegalovirus:
1
...
3
...
5
...
Infectious mononucleosis (heterophile antibody-negative)
...
Fever with abnormalities in hematological parameters
...
From mother to baby:
• Transplacental
• From birth canal of infected mother during delivery of fetus
...
2
...
3
...
4
...
Q
...
Laboratory diagnosis of Cytomegalovirus:
1
...
2
...
3
...
4
...
• Detection of viral IgG indicates past infection
...
Q
...
Cytomegalic inclusion disease: Cytomegalic inclusion disease is a generalized infection of infants caused by
intrauterine or early postnatal infection with the cytomegalovirus
...
Characteristics:
1
...
3
...
It is characterized by multinucleated giant cells with prominent owl’s eye shaped intra-nuclear inclusion
bodies
...
Infection of the fetus occurs mainly in pregnant women with primary infection of CMV
...
Clinical features of cytomegalic inclusion disease:
1
...
3
...
5
...
Microcephaly
Seizures
Deafness
Jaundice
Purpura
Hepatosplenomegaly
29
7
...
Intra-uterine growth retardation
...
Q
...
Epstein Barr Virus (EBV)
EBV is an oncogenic virus; it can transform the normal cell to malignant cell
...
g
...
Pathogenesis:
EBV is commonly transmitted by infected saliva and initiates infection in the oropharynx
...
↓
Infected B cells spread the infection from the oropharynx throughout the body
...
The T cells are the atypical lymphs seen in the blood
smear
...
↓
EBV infected B cells synthesize immunoglobulin
...
g
...
↓
Infectious mononucleosis
...
These are usually clinically
silent, sometimes with serious consequences
...
Usually we use sheep cell antigen to detect the antibody
...
Infectious mononucleosis:
a
...
b
...
c
...
d
...
e
...
f
...
2
...
3
...
30
4
...
Laboratory diagnosis of infectious mononucleosis: Diagnose is based on two approaches:
1
...
Absolute lymphoctosis
b
...
They are large and have a lobulated nucleus and a vacuolated, basophilic cytoplasm
...
Immunologic or serologic approach:
a
...
b
...
• IgM VCA antibody response: It detects early illness
...
Treatment:
•
•
•
No viral therapy is necessary for uncomplicated infectious mononucleosis
...
Adoptive transfer of EBV – reactive T cells in EBV related lymphoproliferative disease
...
Q
...
He suspected as a case of infectious mononucleosis
...
Name the causative agent
...
Mention a serological test you will advise for the diagnosis
...
Write two cancers produced by this virus
...
Serologic tests:
1
...
They
are large and have a lobulated nucleus and a vacuolated, basophilic cytoplasm
...
Immunologic or serologic approach:
a
...
b
...
• IgM VCA antibody response: It detects early illness
...
Cancers: Burkitt’s lymphoma, nasophayngeal carcinoma, lymphomas and gastric carcinoma
...
Mode of transmission: Via oral secretions
...
Clinical findings:
31
1
...
3
...
Exanthum subitum (roseola infantum or sixth disease) is the mild common childhood disease
characterized by high fever and skin rash
...
Human Herpesvirus 7
Human herpesvirus 7 is a T lymphocytic human herpesvirus
...
Most infections of HHV 7 occur in childhood
...
Similar to human herpesvirus 6, primary infection with human herpesvirus 7 has been linked with roseola infantum
in infants and young children
...
KSHV is lymphotropic virus
...
Pathogenesis: HHV-8 causes malignant transformation by inactivation of tumor suppressor gene
...
Route of transmission:
1
...
Contact with oral secretions is likely the most common route of transmission
...
Laboratory diagnosis:
1
...
3
...
Laboratory diagnosis of KS is often made by biopsy of the skin lesions
...
Serologic tests measure persistent antibody to KSHV, using indirect immunofluorescence, Western blot
and ELISA
...
Treatment:
•
•
Surgical excision, radiation and systemic drugs, such as alpha interferon or vinblastine, can be used
...
DNA Non-Enveloped Viruses
DNA non-enveloped viruses:
1
...
3
...
Important properties of adenoviruses:
1
...
3
...
5
...
Virion: Icosahedral
...
Proteins: Important antigens (hexon, pentose base, fiber) in outer capsid proteins
...
Diseases:
1
...
3
...
5
...
Eye infections:
a
...
Keratoconjunctivitis
Hemorrhagic cystitis
Gastroenteritis
Some adenoviruses cause sarcomas in rodents
...
2
...
Aerosol droplet
Fecal – oral route: The fecal-oral route is the most common mode of transmission among young children
and their families
...
Epidemiology: Outbreaks occur among military recruits, apparently as a result of the close living conditions that
facilitate transmission
...
g
...
Group C viruses persist as latent infections for years in adenoids and tonsils and are shed in the feces for
many months after the initial infection
...
Laboratory diagnosis:
•
•
Isolation of the virus in the cell culture
...
Treatment: There is no antiviral therapy
...
33
Papillomaviruses
Human Papillomavirus (HPV)
Diseases:
1
...
Papillomas (benign tumors of squamash cells) e
...
, skin warts, planter warts, flat warts, anogenital warts,
laryngeal papillomas
...
Important properties of Papillomaviruses:
1
...
3
...
5
...
Genome: Double stranded DNA, circular
...
Stimulate cell DNA synthesis
...
Restricted host range and tissue tropism
...
Significant cause of human cancer, especially cervical cancer
...
Viral oncoproteins intact with cellular tumor suppressor proteins
...
2
...
Genital warts are among the most common sexually
transmitted diseases
...
Pathogenesis: Papillomaviruses infect squamous epithelial cells and induce within those cells a characteristic
cytoplasmic vacuole
...
The proteins encoded by viral genes E6 and E7 interfere with the growth-inhibitory activity of the proteins encoded
by the p53 and RB tumor suppressor genes and thereby contribute to oncogenesis by these viruses
...
Why type 16 papillomavirus causes carcinomas most frequently?
The E6 and E7 proteins of HPV type 16 bind more strongly to p53 and RB proteins than the E6 and E7 proteins of
HPV types not implicated in carcinomas – a finding that explains why type 16 causes carcinomas more frequently
than the other types
...
2
...
4
...
The presence of koilocytes in the lesions indicates HPV infection
...
Diagnostic tests based on detection of antibodies in a patient’s serum or on isolation of the virus from a
patient’s tissue are not used
...
Skin warts: Liquid nitrogen
...
Severe HPV infections: Cidofovir
...
2
...
Vaccination: A recombinant vaccine against four types of HPV is available
...
It is approved for use in female patients between the age of 9 and 26 years
...
The vaccine gives immunity for at least 5 years
...
Circumcision reduces the risk of infection by HPV
...
2
...
4
...
2
...
Parvovirus B19 is a very small non-enveloped virus with single stranded DNA genome
...
There is no serotype
...
2
...
B19 virus is transmitted primarily by the respiratory route
...
Blood transfusions
...
Pathogenesis:
•
•
•
B19 virus primarily infects two types of cells: red blood precursors (erythroblasts) in the bone marrow,
which accounts for the aplastic anemia and endothelial cells in the blood vessels, which accounts, in part,
for the rash associated with erythema infectiosum
...
Hydrops fetalis manifests as massive edema of the fetus
...
Laboratory diagnosis:
1
...
3
...
Fifth disease and aplastic anemia are usually diagnosed by detecting IgM antibodies
...
In immunocompromised patients, viral DNA in the blood can be assayed by PCR
...
Treatment and prevention:
•
•
•
There is no specific treatment of B19 infection
...
There is no vaccine or chemoprophylaxis
...
2
...
4
...
6
...
Orthomyxoviruses – influenza type A, B, C
...
Influenza viruses are important human pathogens because they cause both outbreaks of
influenza that sicken and kill thousands of people each year as well as infrequent devastating worldwide epidemics
(pandemics)
...
What are the myoxviruses? Why are they so called?
Myxoviruses include Orthomyxoviruses and Paramyxoviruses
...
These viruses attack mucin
layer
...
Q
...
Classification of Orthomyxoviruses: Influenza viruses are the only members of the Orthomyxovirus family
...
Influenza A
2
...
Influenza C
Diseases
Worldwide epidemics (pandemics) of influenza
...
Mild respiratory tract infections but does not cause outbreaks of influenza
...
What are the important characteristics of Orthomyxoviruses?
Important properties of Orthomyxoviruses:
1
...
3
...
5
...
Virion: Spherical, pleomorphic, helical nucleocapsid
...
Proteins: Nine structural proteins, one nonstructural
...
replication: Nuclear transcription
...
• Influenza viruses cause worldwide epidemics
...
Mention the comparisons between Orthomyxoviruses and Paramyxoviruses
...
Properties
Viruses
Orthomyxoviruses
Influenza A, B and C viruses
...
Genome
3
...
5
...
7
...
Yes
Paramyxoviruses
Measles, mumps and respiratory
syncytial and parainfluenza viruses
...
Yes
8
...
Giant cell formation
Antigenic stability
Helical
Yes
Smaller (110 nm)
Hemagglutinin and neuraminidase in
different spikes
...
Yes
Stable
38
10
...
Site
for
RNP
formation
9 nm
18 nm
Nucleus
Cytoplasm
Features of viruses that infect the respiratory tract:
Virus
RNA viruses
1
...
Parainfluenza
virus
3
...
Rubella
virus
5
...
Mumps
virus
7
...
coronavirus
9
...
Herpes
simplex virus
type 1
2
...
Varicella
Zoster virus
Disease
Number
of
serotypes
Lifelong
immunity
of disease
Vaccine
available
Viral
latency
Influenza
Many
No
Croup
Many
No
-
-
Amantadine,
rimantadine,
oseltamivir,
zanamivir
None
Bronchitis
Two
Incomplete
-
-
Ribavirin
Rubella
One
Yes
+
-
None
Measles
One
Yes
+
-
None
Parotitis,
meningitis
Common cold
Common
cold,
SARS
Herpangina,
pleurodynia,
myocarditis
One
Yes
+
-
None
Many
Three
No
No
-
-
None
None
Many
No
-
-
None
Gingivosmomatitis
One
No
-
+
Infectious
mononucleosis
Chicken
pox,
shingles
One
Yes
-
+
One
Yes
-
+
No
-
+
4
...
+
Treatment
-
Acyclovir
in
immunodeficient
patients
None
Acyclovir
in
immunodeficient
patients
None
Q
...
Hemagglutinin (HA):
1
...
3
...
Hemagglutinin derives its name from its ability to agglutinate erythrocytes under certain conditions
...
Influenza A virus has 16 antigenically distinct types of HA
...
5
...
Variability in HA is primarily responsible for the continual evolution of new strains and
subsequent influenza epidemics
...
In the clinical laboratory, HA agglutinates RBC, which is the basis of a diagnostic test called the
hemagglutinin inhibition test
...
Influenza A virus has 9 antigenically distinct types of NA
...
Function:
a
...
b
...
This enhances the ability of
the virus to gain access to the respiratory epithelial cells
...
It helps prevent self-aggregation of virus by removing sialic acid residues from viral glycoproteins
...
Write short note on:
•
•
Antigenic shift
Antigenic drift
Antigenic shift: Antigenic shift is the process by which two or more different strains of a virus or strains of two or
more different viruses combine to form a new subtype having a mixture of the surface antigens of the two or more
original strains
...
Antigenic shift is a specific case of
reassortment or viral shift that confers a phenotypic change
...
Affected species include
other mammals and birds, giving influenza A the opportunity for a major reorganization of surface antigens
...
Importance: Antigenic shift is important for the emergence of new viral pathogens as it is a pathway that viruses
may follow to enter a new niche
...
Due to the
structure of its genome, HIV does not undergo reassortment, but it does recombine freely and via superinfection
HIV can produce recombinant HIV strains that differ significantly from their ancestors
...
This results in a new strain of virus particles which cannot be
inhibited as effectively by the antibodies that were originally targeted against previous strains, making it easier for
the virus to spread throughout a partially immune population
...
Mechanism: Antigenic drift is due to the accumulation of point mutations in the gene, resulting in amino acid
changes in the protein
...
Importance: The immune system recognizes viruses when antigens on the surfaces of virus particles bind to
immune receptors that are specific for these antigens
...
After an infection,
the body produces many more of these virus-specific immune receptors, which prevent re-infection by this particular
strain of the virus and produce acquired immunity
...
However, viral genomes are constantly mutating,
producing new forms of these antigens
...
Q
...
Epidemics and pandemics (worldwide epidemics) occur when the antigenicity of
the virus has changed sufficiently that the preexisting immunity of many people is no longer effective
...
Influenza B virus does not cause pandemics – Explain
...
The antigenic changes
exhibited by influenza B virus are less dramatic and less frequent than those of influenza A virus
...
Transmission: The virus is transmitted by airborne droplets
...
↓
Neuraminidase degrades the protective mucus layer
...
↓
The infection is limited primarily to the respiratory tract
...
↓
Influenza virus pneumonia, which can complete influenza, is interstitial in location
...
2
...
4
...
Severe myalgias (muscle pains) coupled with respiratory tract symptoms are typical of influenza
...
The symptoms usually resolve spontaneously in 4 to 7 days
...
2
...
Reye’s syndrome
...
It is characterized by encephalopathy and liver degeneration
...
Laboratory diagnosis of influenza:
Specimens:
•
•
•
Nasal washings
Gargles
Throat swabs
Specimens should be obtained within 3 days after the onset of symptoms
...
RT-PCR is rapid (>1 day), sensitive and specific
...
Viral isolates can be identified by hemagglutination inhibition
...
It is used to make a retrospective diagnosis
...
41
Treatment of influenza:
•
•
Oseltamivir and Zanamivir: For both influenza A and B
...
Amantadine and rimantadine: For influenza A
...
Prevention of influenza:
•
•
•
Vaccination: Vaccine consists of influenza A and B viruses, typically two A strains and one B strain
...
The vaccine is usually reformulated each year
to contain the current antigenic strains
...
Proteolytic drugs: Amantadine, rimantadine and oseltamivir
...
42
Paramyxoviruses
The paramyxoviruses include:
1
...
3
...
Measles
Mumps
Respiratory syncytial virus
Parainfluenza viruses
Important properties of Paramyxoviruses:
1
...
3
...
Genome: Single stranded RNA, linear, non-segmented, negative sense, non-infectious
...
4
...
5
...
Envelope spikes of paramyxoviruses:
Virus
Measles virus
Mumps virus
Respiratory syncytial virus
Parainfluenza virus
Hemagglutinin
Neuraminidase
+
+
-
+
+
Fusion protein
+
+
+
+
Measles virus
Disease: Measles, characterized by a maculopapular rash
...
Transmission: Measles virus is transmitted via respiratory droplets produced by coughing and sneezing
...
Both IgG antibody and cell mediated immunity
give protection
...
Q
...
Pathogenesis of measles:
Virus infects cells lining the upper respiratory tract
...
Cytotoxic T cells attack the measles virus infected vascular endothelial cells in the skin
...
↓
Development of rash
↓
Multinucleated giant cells, which form as a result of the fusion protein in the spikes, are characteristic of the lesions
...
What are the clinical features of measles?
Clinical features of measles:
43
1
...
3
...
5
...
Prodromal phase: Fever, conjunctivitis (causing photophobia), running nose and coughing
...
It is the
pathognomonic sign of measles
...
The rash develops a brownish hue several days later
...
Some important information on measles:
•
•
•
•
•
Disease is more severe and prolonged in adults
...
g
...
Supplementation of vitamin A greatly reduces the severity of measles
...
Death usually results from bacterial superinfection such as pneumonia, diarrheal disease or
noma/cancrum oris
...
Mention the complications of measles
...
2
...
4
...
6
...
Encephalitis (1 per 1000 cases of measles)
Primary measles (giant cell) pneumonia
...
Subacute sclerosing panencephalitis (SSPE): It is rare, fatal disease of the CNS that occurs several years
after measles
...
Measles virus infection of the fetus typically causes fetal death
...
The virus can be isolated in cell culture
...
g
...
Treatment: There is no antiviral therapy available
...
It is given subcutaneously to children
as 15 months of age, usually in combination with rubella and mumps vaccine
...
Q
...
a
...
What may be the effect of such infection in fetus?
c
...
2
...
Fetal death
...
The vaccine should not be given to
44
children prior to 9 months of age, because maternal antibody in the child can neutralize the virus and reduce the
immune response
...
A girl of 9 years old presented with rash in the whole body
...
What would be
your differential diagnosis?
Differential diagnosis of fever with rash:
1
...
3
...
5
...
7
...
Chikungunya
Dengue
Spotted or typhus group rickettsiosis
...
Mumps Virus
Disease: The virus causes mumps, a systemic viral infection characterized by parotid gland swelling
...
Transmission: Mumps virus is transmitted via respiratory droplets
...
Alternatively, the virus may ascend from the buccal
mucosa up Stensen’s duct to the parotid gland
...
Mumps occur only once
...
Clinical findings:
1
...
3
...
5
...
Fever, malaise and anorexia
...
Characteristic increase in parotid pain when drinking citrus juices
...
Q
...
Complications of mumps:
Frequent
•
•
•
•
Orchitis
Oophoritis
Pancreatitis
Abortion
Rare
•
•
•
•
•
•
•
•
Bilateral orchitis leading to
sterility
Nerve deafness
Arthritis
Labyrinthitis
Myocarditis
Meningitis
Encephalitis
Hydrocephalus
Laboratory diagnosis: The diagnosis of mumps is usually made clinically, but laboratory tests are available for
confirmation
...
2
...
A fourfold rise in antibody titer in either the hemagglutination inhibition or CFT is diagnostic
...
• Antibody to V antigen indicates past infection
...
Skin test based on delayed hypersensitivity detects previous infection
...
Treatment: There is no antiviral therapy for mumps
...
Because it is a live vaccine, it
should not be given to immunocompromised persons or pregnant women
...
This is
followed by parenchymal inflammation and perivascular interstitial lymphocyte infiltration, leading to orchitis,
oophoritis
...
2
...
Pneumonia and bronchitis in infants
...
Pneumonia in the elderly and in patients with chronic cardiopulmonary diseases
...
Pathogenesis:
•
•
•
RSV infection in infants is more severe and more often involves the lower respiratory tract than in older
children and adults
...
Immunopathogenesis: Maternal antibody passed to the infant may react with the virus, form immune
complexes and damage respiratory tract cells
...
Laboratory diagnosis:
1
...
3
...
5
...
Detection of the presence of virus by immunofluorescence or smears of respiratory epithelium
...
A rise in antibody titer of at least four fold is also diagnostic
...
Treatment:
•
•
Aerosolized ribavirin is recommended for severely ill-hospitalized infants
...
Prevention:
•
•
•
•
There is no vaccine
...
Hyper immunoglobulins for infants and children with chronic lung disease
...
46
Parainfluenza Viruses
Diseases:
•
•
In children: Croup (acute laryngotracheobronchitis), laryngitis, bronchiolitis and pneumonia
...
Transmission: These viruses are transmitted via respiratory droplets
...
A large proportions
of infections are subclinical
...
Clinical findings:
•
•
Croup occurs in children younger than 5 years of age
...
Laboratory diagnosis:
•
•
Most infections are diagnosed clinically
...
Treatment and prevention: There is no antiviral therapy nor a vaccine available
...
2
...
2
...
4
...
6
...
It is composed of one piece of single stranded RNA, an icosahedral nucleocapsid, and a lipoprotein
envelope
...
Its surface spikes contain hemagglutinin
...
The virus has a single antigenic type
...
Transmission: The virus is transmitted via respiratory droplets and from mother to fetus transplacentally
...
↓
From there it spreads via the blood to the internal organs and skin
...
Immunity: Natural infection leads to lifelong immunity
...
Antibody crosses the
placenta and protects the newborn
...
2
...
Fever and malaise is followed by maculopapular rash, which starts on the face and progresses downward
to involve the extremities
...
Posterior auricular lymphadenopathy is characteristic
...
Q
...
Complications of rubella virus:
1
...
3
...
Congenital rubella syndrome (CRS)
...
What is congenital rubella syndrome?
Congenital rubella syndrome: The rubella virus acts as a teratogen
...
Clinical features of CRS:
1
...
Treatment effects of infants: Growth retardation, rash, hepatosplenomegaly, jaundice and
meningoencephalitis
...
a
...
48
3
...
b
...
Classic triad of CRS: Cataracts, cardiac abnormalities e
...
, parent ductus arteriosus and deafness
...
Treatment, prevention and control: There is no specific treatment for congenital rubella
...
Prevention: Prevention involves immunization with the live, attenuated vaccine
...
It is given subcutaneously to children at 15 months of age (usually in combination with
measles and mumps vaccine) and to immunized young adult women if they are not pregnant and will use
contraception for the next 3 months
...
1:8 or greater titer of IgG antibody indicates immunity and consequent protection of the fetus
...
49
Rabies Virus
Rabies virus is a Rhabdovirus
...
Important properties:
1
...
3
...
5
...
Because the genome RNA has negative polarity, the virion contains an RNA dependent RNA polymerase
...
Rabies virus has a broad host range
...
Replication: Cytoplasm; virions bud from plasma membrane
...
Mention the mode of transmission of rabies virus
...
2
...
The virus is transmitted by the bite of a rabid animal that manifests aggressive, biting behavior induced by
the viral encephalitis e
...
, bite of dogs, cats
...
Non-bite exposures: Exposures to aerosols of bat secretions containing rabies virus
...
Q
...
Rabies: Rabies is an acute infection of the CNS by rabies virus that is almost always fatal
...
Although the number of human cases is small, rabies in a
major public health problem because it is widespread among animal reservoirs
...
↓
The virus multiplies locally at the bite site
...
During its transport within the nerve, the virus is
sheltered from the immune system and little, if any, immune response occurs
...
↓
Within the CNS, encephalitis develops, with the death of neurons and demyelination
...
↓
From the CNS, the virus travels down the peripheral nerves to the salivary glands and other organs
...
There is no viremic stage
...
Write short note on: Negri body
...
Negri bodies are filled with viral nucleocapsids
...
Therefore, the absence of Negri bodies does not rule out rabies as a
diagnosis
...
What are the main reservoirs of rabies virus?
50
Main reservoirs of rabies virus:
1
...
3
...
5
...
7
...
Dogs (99% cases in Bangladesh)
...
Mention the condition on which the incubation period of rabies depends
...
It is shorter when bites are sustained on the head rather than on the leg, because
the virus has a shorter distance to travel to reach the central nervous system
...
The clinical spectrum ca be divided into
three phases:
1
...
3
...
An acute neurologic phase (2 – 7 days): Signs of nervous system dysfunction such as a nervousness,
apprehension, hallucinations and bizarre behavior
...
The act of swallowing
precipitates a painful spasm of the throat muscles
...
There may
be aerophobia (fear when feeling a breeze)
...
The major cause of death is respiratory paralysis
...
Give a laboratory diagnosis of rabies
...
Examination of brain tissue by using either fluorescent antibody to rabies virus or histologic staining of
Negri bodies in the hippocampal neurons
...
2
...
2
...
4
...
Isolation of the virus from sources such as saliva, spinal fluid and brain tissues
...
Negri bodies can be demonstrated in corneal scrapings and in autopsy specimens of the brain
...
What do you mean by a street virus?
Street virus: Freshly isolated virulent virus from rabid animals in the laboratory is called street virus
...
2
...
4
...
6
...
The virus, as it occurs in nature is known street
virus
...
‘
It is pathogenic to all animals
...
It has long and variable incubation periods (usually 21 – 60 days in dogs)
...
Q
...
Criteria:
1
...
3
...
5
...
7
...
The fixed or mutant virus multiplies rapidly
...
Direct injection to brain produces encephalitis
...
It is used to prepare anti-rabies vaccine (ARV)
...
It may be pathogenic, if rabies vaccine (prepared from fixed virus) is injected after
inadequate inactivation of virus
...
Give the differences between street virus and fixed virus
...
2
...
4
...
6
...
It can multiply in the neuronal and extraneuronal tissue
...
Regularly produces Negri bodies
...
It cannot be used to make vaccine
...
Fixed virus
Serial brain to brain passage of a street virus in
rabbits produces a fixed virus
...
3
...
5
...
Incubation period: Short and fixed
...
It is non-pathogenic
...
1
...
Only supportive treatment is available
...
How can you prevent post exposure rabies?
Management of human rabies or management of rabid dog bite:
Wound management:
1
...
3
...
Cleaning of the wound
...
Suturing is needed
...
Post exposure immunization:
Post exposure immunization involves the use of both1
...
Active immunization: By vaccine (preferably human diploid cell vaccine, HDCV)
...
Passive immunization: By human rabies immune globulin (RIG)
...
Decision to give post-exposure immunization depends on a variety of factors such as1
...
3
...
Whether an attack by domestic animal was provoked, whether the animal was immunized adequately,
and whether the animal is available to be observed
...
Q
...
Prevention of rabies: There are two approaches to prevention of rabies in humans:
52
•
•
Exposure and
Post-exposure
Pre-exposure prophylaxis: Pre-exposure immunization with rabies vaccine should be given to individuals in highrisk groups, such as veterinaries, zookeepers and travelers to areas of hyper endemic infection areas e
...
, Peace
corps members
...
Booster doses
are given as needed to maintain an antibody titer of 1:5
...
Name the diseases where post exposure vaccination is given and why?
Diseases where post exposure vaccination is given:
•
•
•
Rabies
Tetanus
Diphtheria
Post exposure vaccination is given to neutralize and the bacterial toxin
...
Write short note on: Rabies vaccine
...
Types of rabies vaccine: All vaccines for human use contain only inactivated rabies virus
...
Human Diploid Cell Vaccine (HDCV): Rabies virus is grown in the MRC-5 human diploid cell line
...
2
...
3
...
4
...
Disadvantages:
i
...
ii
...
iii
...
05%)
...
Efficiency in persons bitten by rabid animals varies from 5% to 50%
...
Duck embryo vaccine: It is no longer manufactured
...
It is free from post vaccinal encephalitis
...
Anaphylactic reactions are infrequent
...
i
...
Live attenuated vaccine: Live attenuated viruses adapted to growth in chick embryos are used for animals
but not for humans
...
Rabies immune globulin, human (HRIG): HRIG is prepared from plasma of hyper-immunized with
rabies virus
...
Nice to know:
Technique of administration of nerve tissue vaccine (NTV): The ideal site is anterior abdominal wall
...
•
•
•
Slight risk: 2 ml × 7 days
...
Great risk: 10 ml × 14 days
...
Write short note on: Human diploid cell vaccine
...
The rabies virus
preparation is concentrated by ultrafiltration and inactivated with β-propiolactone
...
On days 0,3,7,14 and 28
...
Site of administration: IM in deltoid muscles (must be given to buttock)
...
2
...
Safe
Potent
No serious anaphylactic or encephalitic reactions have been reported
...
Expensive
...
What are the neurotrophic viruses?
Neurotrophic viruses:
1
...
3
...
5
...
7
...
Once infected with HIV, individuals
remain infected for long life
...
Origin of AIDS: HIV in humans originated from cross species infections by simian viruses in rural Africa, probably
due to direct human contact with infected primate blood
...
Q
...
Here the infected person may not suffer from
any symptoms associated with infection
...
Synonym: LAV, HTLV-3 (Human T Lymphocytic Virus 3)
...
2
...
2
...
Incubation period: 6 months to 6 years or more
...
2
...
4
...
Asymptomatic infection
...
AIDS (slime disease) and ARC
...
2
...
4
...
6
...
It breaks down the body’s immune system and leads to a fatal illness known as AIDS
...
Neurological disorders may develop
...
Chronic diarrhea > 1 month
...
Weight loss > 10% in last month
...
Mention the differences between HIV-1 and HIV-2
...
5
...
7
...
2
...
1
...
3
...
5
...
7
...
5
...
Long
Not so common
...
7
...
Carry a vpx gene
...
2
...
Short
Kaposi sarcoma is more
common
...
Carry a vpu gene
...
Mention the important properties of HIV
...
HIV belongs to the lentivirus subgroup of retroviruses, which cause slow infections with long incubation
period
...
Virion: Spherical, cylindrical core
...
Genome: Single stranded RNA, linear, positive polarity, diploid
...
Proteins: Envelope glycoprotein, reverse transcriptase enzyme, protease
...
Envelope: Present
...
Replication: Reverse transcriptase makes DNA copy from genomic RNA; provirus DNA is template for
viral RNA
...
Maturation: Particles bud from plasma membrane
...
Important antigens of HIV:
• Envelope Ag:
a
...
gp 41
c
...
• Nucleocapsid core protein:
a
...
P17
Q
...
Major genes and their protein products of HIV:
Gene
Proteins encoded by gene
Structural genes found in all retroviruses
P24, p7
gag
P17
Reverse transcriptase
Functions of proteins
Nucleocapsid
Matrix
Transcribes RNA genome into DNA
55
Protease
Cleaves precursor polypeptides
Integrase
Integrates viral DNA into host cell DNA
gp120
Attachment to CD4 protein
env
gp41
Fusion with host cell
...
tat
rev
Transport of late mRNAs from nucleus to cytoplasm
...
vif
Enhances infectivity by inhibiting the hypermutation in retroviral DNA
...
vpr
vpu
Enhances virion release from cell
...
Describe the replication of HIV
...
2
...
4
...
6
...
8
...
HIV binds with the CD4 receptor on the surface of CD4+ helper T cells through their gp120 proteins
...
↓
Next the virion gp41 protein mediates fusion of the viral envelope with the cell membrane
...
↓
Reverse transcription: In the cytoplasm, reverse transcriptase transcribes the genome RNA into double
stranded DNA
...
Integrated viral DNA is called proviral DNA
...
Translation: Viral mRNA is translated into several large polyproteins
...
• gag polyprotein is cleaved to form p27, p17
...
Assembly: Viral proteins then migrate to the cell surface and are assembled with genome RNA to produce
infectious virus particles
...
Q
...
Mode of transmission of HIV:
1
...
• Heterosexual
...
Parenteral transmission:
• By blood and blood products
...
• By drug abusers
...
Vertical transmission:
• Transplacental
• During birth
• Breast feeding
4
...
Any skin piercing such as injection, ear and nose piercing, tattooing, acupuncture
...
57
Q
...
Pathogenesis of HIV infection:
Through different routes, HIV enters into the bloodstream
...
The death of CD4+ cells may be due to• The fusion of HIV infected cells mediated by gp41 form multinucleated giant cells (MNGC) which are
non-functioning
...
• HIV may act as a superantigen, which activates many helper T cells and leads to their demise
...
↓
The consequences of CD4+ helper T cell dysfunction caused by HIV infection are devastating because the helper
T cell plays a central and critical role in the human immune response
...
But suppression of CMI is more marked
(immunosuppression)
...
↓
AIDS
HIV also infects brain monocytes and macrophages which contain CD4 proteins on their surface causing
neuropsychiatric manifestations
...
Nice to know:
Immune response to HIV infection: The main immune response to HIV infection consists of cytotoxic CD8+
lymphocytes
...
It is the ultimate failure of
these cytotoxic T cells that results in the clinical picture of AIDS
...
Antibodies against various HIV proteins such as p24, gp120 and gp41 are produced, but they mineralize the virus
poorly in vivo and appear to have little effect on the course of the disease
...
How does HIV evade the immune system?
HIV has three main mechanisms by which it evades the immune system
...
2
...
Integration of viral DNA into host cell DNA, resulting in a persistent infection
...
The production of tat and nef proteins that downregulate class I MHC proteins required for cytotoxic T
cells to recognize and kill HIV infected cells
...
Q
...
This seems likely to be the result of integration of
viral DNA into the DNA of infected cells
...
Describe the stages in the course of HIV infection
...
An early acute stage: Usually begins 2 to 4 weeks after infection
...
A maculopapular rash on the trunk, arms and legs (but sparing
the palms and soles) is also seen
...
Leukopenia
2
...
3
...
4
...
5
...
6
...
B
...
In
untreated patients, the latent period usually lasts for 7 to 11 years
...
The patient is asymptomatic during this period
...
Viremia is low or absent
...
A large amount of HIV being produced by lymph node cells but remains sequestered within
the lymph nodes
...
4
...
C
...
Q
...
AIDS related complex (ARC): A syndrome called AIDS related complex can occur during the latent period of
HIV infection
...
Cause of ARC: ARC is caused by damage to the immune system, not by the opportunistic infections and cancers
associated with AIDS
...
2
...
4
...
6
...
Unexplained diarrhea lasting longer than a month
...
Malaise
...
Fever
...
Other middle opportunistic infections such as oral thrush, generalized lymphadenopathy or enlarged
spleen
...
Nice to know:
Opportunistic infections in AIDS: The predominant causes of morbidity and mortality among AIDS patients are
opportunistic infections, i
...
, severe infections induced by agents that rarely cause serious disease in immune
competent individuals
...
Causes of opportunistic infections in AIDS: HIV infects CD4+ T cells
...
So both the cell mediated and antibody
mediated immunity is lost
...
Q
...
Lab diagnosis of AIDS:
59
Principle: AIDS is diagnosed by serological test for antibody detection against the HIV
...
Specimen collection: Blood for serological test and culture
...
Serological tests or detection of antibody:
• ELISA: ELISA detects anti HIV antibodies and gives presumptive diagnosis of HIV infection
...
• Western blot: The most widely used confirmatory test is the Western blot technique, which
detects antibodies to HIV proteins including p24, gp41, gp120 or gp160
...
3
...
5
...
HIV infection for longer than 6
months without a detectable antibody is very uncommon
...
PCR also can
detect viral RNA load which is an important marker of disease progression and prognosis
...
Detection of viral antigen: Low levels of circulating HIV-1 p24 antigen can be detected in the plasma by
EIA soon after infection
...
g
...
Preventive measures for HIV: No vaccine is available
...
Prevention of sexual transmission:
1
...
2
...
3
...
4
...
5
...
6
...
7
...
8
...
B
...
Blood product transmission: Donor questionnaire, routine screening of donated blood, blood
substitute use
...
Injection drug use: Education, needle/syringe exchange, avoidance of shooting galleries,
sharing and support for methadone maintenance programs
...
Perinatal:
1
...
2
...
3
...
D
...
Education or training: Universal precautions, needle stich avoidance
...
Post exposure prophylaxis
...
2
...
4
...
6
...
Genome: Single stranded RNA, linear
...
e
...
Replication: Replication occurs in the cytoplasm
...
The picornavirus family includes two groups of medical importance
...
Enteroviruses: Enteroviruses infect primarily the enteric tract
...
Polio virus
b
...
Echoviruses
d
...
Rhinoviruses: Rhinoviruses are found in the nose and throat (rhino means nose)
...
Properties:
1
...
3
...
5
...
Three antigenic types designated as type 1,2,3
...
Cytoplasmic replication
...
Transmission: Poliovirus is transmitted by the fecal oral route
...
Q
...
Pathogenesis of poliomyelitis:
61
Vaccine
available
+
+
Antiviral
therapy
-
-
-
-
-
Causative agent: Polio virus
...
Incubation period: 7 to 10 days
...
↓
Multiplies in the lymphoid tissue of the oropharynx and small intestine (Payer’s patches)
...
It can also spread retrograde along nerve axons
...
↓
Death of the anterior horn neurons
↓
Paralysis of the muscles innervated by those neurons
...
Nice to know:
Immunity against polio virus: Infection provides lifelong type-specific immunity
...
Clinical findings of poliomyelitis: The incubation period is usually 10 to 14 days
...
2
...
4
...
Unapparent, asymptomatic infection: Asymptomatic infection is quite common
...
Abortive poliomyelitis: It is the most common clinical form characterized by mild fever, headache, sore
throat, nausea and vomiting
...
Non apparent poliomyelitis: Manifests are aseptic meningitis with fever, headache and a stiff neck
...
Paralytic poliomyelitis: In paralytic poliomyelitis, flaccid paralysis is the predominant finding, but brain
stem involvement can lead to life threatening respiratory paralysis
...
The
motor nerve damage is permanent, but some recovery of muscle function occurs as other nerve cells take
over
...
If the spinal cord is also involved, the term meningomyeloencephalitis is often used
...
Marked
deteriorations of the residual function of the affected muscles occurs many years after the acute phase
...
No permanent carrier state occurs following infection by poliovirus, but virus excretion in the feces can occur for
several months
...
Virus can be recovered from throat, stool or CSF by inoculation of the cell culture
...
Treatment:
•
•
•
There is no antiviral therapy
...
Physiotherapy for the affected muscles is important
...
Write down the prevention of poliomyelitis
...
2
...
Oral polio vaccine or Sabin vaccine or live attenuated polio vaccine
...
Both the killed and the live vaccines contain all three serotypes
...
1
...
Live attenuated vaccine (Sabin): Dose schedule1st at birth
2nd – 6 weeks after birth
...
4th – 14 weeks later after birth
...
Inactivated or killed vaccine (Salk): At first 3 doses are given at intervals of 1-2 months and 4th dose 6-12
months after that
...
How does oral polio vaccine prevent poliomyelitis?
Oral polio vaccine prevents poliomyelitis by1
...
Production of local gut immunity by provoking production of intestinal IgA
...
Q
...
Live attenuated vaccine (Sabin vaccine) or oral polio vaccine:
Advantages:
1
...
3
...
It is cheaper
...
Produce local gut immunity by provoking production of intestinal IgA
...
Disadvantages:
1
...
3
...
5
...
7
...
Infection of the GIT by other enteroviruses can limit replication of the vaccine virus and reduce protection
...
Cannot be given in pregnancy
...
Multiple doses are necessary to establish immunity
...
Nice to know:
Enhanced polio vaccine or eIPV: The current version of the inactivated vaccine is called enhanced polio vaccine
...
It also induces
mucosal immunity like IgA, making it capable of interrupting transmission
...
Compare and contrast different types of polio vaccine
...
Can cause disease in the immunocompromised
patients
10
...
Requires refrigeration
12
...
2
...
4
...
6
...
8
...
Important properties:
1
...
3
...
5
...
Genome: Double stranded RNA, linear, segmented (10-12 segments)
...
Replication: In the cytoplasm
...
Serotypes: There are at least 6 serotypes of human rotaviruses
...
7
...
• Major cause of infantile diarrhea
...
Q
...
Pathogenesis of rotavirus infection:
Rotaviruses infect cells in the villi of the small intestine (gastric and colonic mucosa are spared)
...
↓
One of the rotavirus encoded proteins, NSP 4, is a viral enterotoxin and induces secretion by triggering a signal
transduction pathway
...
Impaired sodium and glucose absorption as
damaged cells on villi are replaced by non-absorbing immature crypt cells
...
Clinical features of rotavirus infection:
1
...
3
...
Watery, non-bloody diarrhea
...
Adults usually have major symptoms
...
Detection of rotavirus in the stool by using radioimmunoassay
...
3
...
Nucleic acid based technique: Polymerase chain reaction
...
Both contain live virus and are given orally
...
Enumerate the viruses that cause hepatitis
...
Of these, five medially important viruses are
commonly described as ‘hepatitis viruses’ because their main site of infection is the liver
...
2
...
4
...
HAV (Hepatitis A virus)
HBV (Hepatitis B virus)
HCV (Hepatitis C virus)
HDV (Hepatitis D virus)
HEV (Hepatitis E virus)
Other viruses responsible for hepatitis: These viruses infect the liver but also infect other sites in the body and
therefore are not exclusively hepatitis viruses
...
2
...
4
...
6
...
Compare hepatitis viruses
...
Sexual
Hepatitis D
Unclassified
Deltavirus
35
nm,
spherical
Yes (HBsAg)
ssRNA
Acid sensitive
Hepatitis E
Hepaviridae
Hepevirus
30-32
nm,
icosahedral
No
ssRNA
Heat stable
Blood, sexual
Fecal oral
Moderate
Rare
Low, regional
Frequent
Regional
In pregnancy
High
Rare
Blood, sexual, at
birth
High
Rare
Never
Often
Often
Often
Never
No
IgM HAV
Yes
HCV Ab
Not known
Ab to delta Ag
No
None
Yes
Yes
HBsAg, HBsAb,
IgM HBcAb
Yes
No
No
No
Yes
Yes
No
No
No
Q
...
What are the seromarkers to be looked for and why?
Laboratory diagnosis of hepatotrophic viruses or viral etiological diagnosis:
Principle: Diagnosis is based on the demonstration of the antibody against the hepatotrophic viruses
...
Specimen collection: Blood
...
• Detection of anti HAV in the serum
...
Hepatitis
Early stage (Acute)
• Presence of HBsAg
...
• Presence of HBeAg
...
Remote past: Presence of anti HBc IgG
...
Resolution: Appearance of anti HBe
...
Serum bilirubin: Raised
...
Alkaline phosphatase: Raised
...
ALT (SGPT) and AST (SGOT): Both are raised
...
Prothrombin time: Prolonged
...
Albumin globulin ratio: Altered
...
Nucleic acid based technique: PCR to detect viral RNA
...
Write down the preventive and control measures for hepatitis
...
2
...
4
...
Creation of awareness
...
HAV: Normal immunoglobulin
...
HBV: Hyper immunoglobulin
...
67
Hepatitis A Virus
Disease: Hepatitis A virus causes hepatitis A
...
2
...
4
...
6
...
HAV is a typical enterovirus classified in the picornavirus family
...
Single stranded RNA virus
...
Replicates in the cytoplasm of the cell
...
It is inactivated by heat
...
It is relatively resistant to most of the disinfectants such as chlorine, UV light and formaldehyde
...
2
...
4
...
Mode of transmission: by fecal oral route
...
Humans are the reservoir for HAV
...
Common source outbreaks arise from fecally contaminated water or food such as oysters grown in polluted
water and eaten raw
...
The virus is transmitted by fecal oral route
...
↓
Portal circulation
...
↓
Cytotoxic T cells attack virus infected hepatocytes and cause the damage to the hepatocytes
...
Immunity: Initially IgM antibody is produced
...
Clinical findings:
1
...
3
...
5
...
The clinical manifestations of hepatitis are virtually the same, regardless of which hepatitis virus is the
cause
...
Dark urine, pale feces and elevated transaminase levels are seen
...
Most HAV infections are asymptomatic and are detected solely by the presence of IgG antibody
...
Q
...
Laboratory diagnosis of hepatitis A virus:
•
•
•
•
Detection of anti HAV IgM antibody is the most important test
...
Detection of anti HAV IgG indicates past infection by HAV
...
Isolation of the virus in cell culture is possible but not available in the clinical laboratory
...
Q
...
Control of reservoir: It is done by1
...
2
...
3
...
B
...
Hand washing after toilet
...
Hand washing before eating
...
Sanitary disposal of excreta
...
Purification of community water supply
...
Vaccination:
• Active immunization: A vaccine containing inactivated HAV is available
...
Susceptible persons travelling to highly endemic area
...
Close personal contacts of patients with HAV
...
To control the outbreak in institutes
...
02 ml/kg body weight
...
2
...
4
...
6
...
8
...
HBV is a member of the hepadnavirus family
...
Virion: Icosahedral nucleocapsid
...
Important antigens: HBsAg, HBcAg and HBeAg
...
The DNA polymerase had both RNA
dependent (reverse transcriptase) and DNA dependent activity
...
Humans are the only natural hosts of HBV
...
Outstanding characteristics: Causes acute and chronic hepatitis, often progressing to permanent carrier
states and hepatocellular carcinoma
...
What are the antigens of HBV?
Different types of hepatitis B virus:
1
...
3
...
Core antigen (HBcAg): The core antigen as the name implies, forms the nucleocapsid core of the virion
...
The e antigen is an
important indicator of transmissibility or infectivity
...
Mention the routes of transmission of HBV
...
Horizontal transmission (10%):
1
...
2
...
3
...
4
...
5
...
69
B
...
Q
...
Pathogenesis of hepatitis B: Pathogenesis depends on cytotoxic T cell mediated immune attack on the liver cells
...
↓
There is no virus induced cytopathic effect on the liver cells
...
Inflammation and necrosis occur
...
g
...
g
...
↓
About 5% of patients with HSV infection become chronic carriers
...
↓
Cirrhosis of liver
...
↓
Development of hepatocellular carcinoma
...
Write down the outcome of hepatitis B virus infection
...
2
...
Subclinical infection: Recovery
...
• Recovery: Recovery from acute HBV infection occurs within 6 months and is characterized by
the appearance of antibody to viral antigens
...
Chronic carrier (>6 months) (5 – 10 %): Persistence of HBsAg beyond 6 months indicates chronic
infection
...
• Chronic active hepatitis leads to cirrhosis and hepatocellular carcinoma and death
...
Give the complications of hepatitis B virus infection
...
2
...
4
...
Chronic active hepatitis
...
Hepatocellular carcinoma
...
Why does hepatocellular carcinoma occur in chronic HBV infection?
The HBV genome has no oncogene and hepatocellular carcinoma appears to be the result of –
1
...
Persistent cellular regeneration that attempts to replace the dead hepatocytes
...
This leads loss of growth control
...
Why does the chronic infection occur in HBV infection?
Causes of chronic HBV infection:
In infants:
1
...
Immune system is less competent and
Deficiency of γ interferon
...
Chronic carriage is more likely to occur when infection occurs in a newborn than in an adult
...
Chronic carriage resulting from neonatal infection is associated with
a high risk of hepatocellular carcinoma
...
Antibody HbsAg (HBsAb) is protective because it binds to surface antigen on the virion and prevents it
from interacting with receptors on the hepatocytes
...
Name the sero-markers of HBV with interpretations
...
Antigens of HBV in the serum:
•
•
HBsAg
HBeAg
Antibodies of HBV in the serum:
•
•
•
Anti HBc IgM
...
Anti HBe IgM
...
HBsAg:
•
HBsAg is an indicator of active infection and a negative test for HBsAg markers HBV infection
very unlikely
...
• Prolonged presence (at least 6 months) of HBsAg indicates carrier state and the risk of chronic
hepatitis and hepatic carcinoma
...
HBeAg: The HBeAg reflects active replication of the virus in the liver
...
That is, HBeAg positive patients are highly infectious
...
Detection of anti HBsAg IgG in blood indicates either a previous infection, in which case anti HBc is
usually also present, or previous vaccination, in which case anti HBc is not present
...
Detection of anti HBc IgM in blood indicates surest marker of active infections
...
Detection of anti HBe IgM in blood indicates recovery and low transmissibility
...
The detection of viral DNA in the serum is strong evidence that infectious virions are present
...
Define window period
...
Window period: It is the period of time between the disappearance of a specific antigen and the appearance of
antibody against that particular antigen
...
This is the window phase
...
Importance of window period in HIV infection: In case of HIV infection, there is a period of several weeks when
HIV antigen has disappeared but antibody is not yet detectable, and therefore diagnosis becomes difficult
...
A patient of jaundice tested for HBsAg and was found negative
...
HBsAg negative does not indicate that the patient is free from hepatitis B virus infection, because patient may be
in window period when HBsAg is not found
...
Q
...
HBsAg: Hepatitis B virus contains glycoprotein on its envelope which is antigenic in character
...
Medical importance: HBsAg is important for laboratory diagnosis and immunization
...
2
...
HBsAg is an important seromarker in hepatitis B virus infection, which appears before the onset of clinical
symptoms, peaks during over disease and then declines to undetectable levels in 3 to 6 months
...
If it is detected after 6 months of initial detection of the same patient, it indicates chronic carrier status of
HBV infection in that patient
...
Write short note on: Anti HBc IgM
...
Importance:
1
...
3
...
In the course disease, it is first detected
...
Detection of anti HBc IgM is the most reliable test for active hepatitis B infection (recent and window
period)
...
Q
...
2
...
4
...
a
...
The vaccine is highly effective in preventing hepatitis B and has few side effects
...
g
...
b
...
HBIG gives immediate, passive protection to individuals known to be exposed to HBsAg
positive blood, e
...
, after an accidental needle stick injury
...
Passive active immunization: Post exposure vaccine (HBsAg) + immunoglobulin (HBIG)
...
Use of sterile syringe and needle
...
Q
...
Post exposure prophylaxis of hepatitis B virus infection: By passive active immunization
...
2
...
The vaccine is highly effective in preventing
hepatitis B and has few side effects
...
HBsAb binds to surface antigen on the virion (HBsAg) and prevents it from interacting with receptors on
the hepatocyte
...
g
...
Nice to know:
Non A, non B hepatitis viruses: The term non A, non b hepatitis was coined to describe the cases of hepatitis for
which existing serologic tests had ruled out all known viral causes
...
In addition, HDV has been described
...
Other viruses which affect the liver include Cytomegalovirus, Epstein
Barr virus, Herpes simplex, chicken pox, measles, rubella and acute HIV infection
...
2
...
4
...
6
...
8
...
HCV is a member of the flavivirus family
...
Genome: Single stranded, positive polarity RNA
...
HCV has at least 6 genotypes and multiple sub-genotypes
...
Strongly predisposes to hepatocellular carcinoma (HCC)
...
Chronic active hepatitis and cirrhosis occurs in 10% of these
...
How HCV is transmitted?
Transmission of HCV:
1
...
3
...
5
...
7
...
Intravenous drug misuse
...
Sexual transmission
...
Latrogenic parental transmission i
...
, contaminated vaccination needles
...
Q
...
Or Give the complications of hepatitis C virus:
Complications of hepatitis C virus:
1
...
3
...
Chronic active hepatitis and cirrhosis of liver (10%)
...
Hepatocellular carcinoma
...
Q
...
2
...
Silent killer – mostly asymptomatic
...
a
...
b
...
c
...
d
...
No vaccine is available, because no antigenic variation of glycoprotein
...
Write down the pathogenesis of hepatitis C virus infection
...
HCV infects hepatocytes primarily
73
↓
There is no virus induced cytopathic effect on the liver cells
...
↓
Chronic active hepatitis
↓
Prolonged liver damage
...
↓
Development of hepatocellular carcinoma
...
How lab diagnosis of HCV infection is done?
Laboratory diagnosis of HCV infection:
Principle: Diagnosis of HCV infection is based on detection of antibody against HCV
...
Steps:
Specimen: blood
...
RIBA (Recombinant Immunoblot Assay): It is the confirmatory test for HCV detection
...
Diagnosis of chronic infection: A chronic infection is characterized by elevated transaminase levels, a positive
RIBA and detectable viral RNA for at least 6 months
...
There is no effective regimen for prophylaxis following needle stick injury; only monitoring is
recommended
...
Important properties:
1
...
3
...
5
...
7
...
HDV is a defective virus
...
Genome: single stranded, negative polarity RNA genome
...
HDV has no virion polymerase
...
e
...
HDV uses the surface antigen of HBV as its enveloped protein
...
74
Q
...
HDV is a defective virus: It is a defective virus, i
...
, it cannot replicate itself, because it does not have the genome
for its envelope protein
...
HBV is therefore the helper virus for HDV
...
e
...
Pathogenesis:
Coinfection of the liver hepatocytes with both hepatitis D and B virus
...
↓
Cytotoxic T cells kill virus infected hepatocytes
...
↓
Hepatitis D
...
2
...
4
...
A person can either be infected with both HDV and HBV at the same time, i
...
, be co-infected or be
previously infected with HBV and then superinfected with HDV
...
Hepatitis in chronic carriers of HBV who become superinfected with HDV is much more severe, and the
incidence of fulminant, life threatening hepatitis, chronic hepatitis and live failure is significantly higher
...
Give the laboratory diagnosis of hepatitis delta virus infection
...
Detection of delta antigen in the patient’s serum
...
Treatment:
•
•
•
There is no specific antiviral therapy against HDV
...
Effective management of hepatitis B effectively prevents hepatitis D
...
Hepatitis E Virus
Hepatitis E: Hepatitis E is a major cause of enterically transmitted hepatitis
...
2
...
HEV is a member of the herpes virus family
...
It is a single stranded RNA virus
...
Clinical features:
75
1
...
3
...
Clinically the disease resembles hepatitis A
...
Hepatitis E differs from hepatitis A in that, infection during pregnancy is associated with the development
of acute liver failure, which has a high mortality
...
Diagnosis:
•
•
In acute infection, IgM antibodies to HEV are positive
...
Treatment and prevention: There is no antiviral treatment and no vaccine
...
Q
...
2
...
4
...
6
...
8
...
Enveloped
...
Human are the reservoir
...
Cytoplasmic replication
...
Viremia is present at the time of fever
...
What is dengue? How dengue virus is transmitted?
Dengue: Dengue is a mosquito borne infection which is caused by dengue virus
...
Mode of transmission: Female Aedes aegypti mosquito transmits the disease from infected person to healthy person
...
Classical dengue fever (dengue fever syndrome)
...
Dengue hemorrhagic fever (DHF)
3
...
Clinical features of classic dengue:
1
...
3
...
5
...
Severe pain in muscles and joints
...
Maculopapular rash
...
Clinical features of dengue hemorrhagic fever: The initial picture is the same as classic dengue, but then shock
and hemorrhage, especially into the gastrointestinal tract and skin, develops
...
Q
...
Dengue hemorrhagic fever: It is a much more severe disease than classical dengue fever, with family rate that
approaches 10%
...
2
...
Then shock and hemorrhage, especially in the GI tract and skin
...
2
...
4
...
Q
...
Pathogenesis of dengue fever:
77
•
Classical dengue fever (first exposure of dengue virus):
Dengue infection by one of the four serotypes
↓
Antibody is formed
↓
Formation of immune complex and activation of complement
↓
Increased vascular permeability and thrombocytopenia
...
The patient recovers from classic dengue caused by one of the four serotypes and antibody against that serotype is
produced
...
↓
An anamnestic, heterotypic response occurs
...
↓
There are two hypotheses about what happens nextImmune complex composed of virus and antibody are formed that activate complement, causing increased vascular
permeability and thrombocytopenia
...
↓
In either scenario, shock and hemorrhage result
...
Write down the laboratory diagnosis of dengue hemorrhagic fever
...
Serological test or antibody detection: The diagnosis is confirmed by detection of IgM antibody or a fourfold or
greater rise in antibody titer in acute and convalescent sera
...
2
...
ELISA
ICT (Immunochromatography test)
Immune blot (Western blot)
Detection of NS1 dengue antigen: ELISA kits to detect the NS1 (non-structural protein) dengue antigen, although
less sensitive than PCR, are becoming more widely available in endemic area
...
Nucleic acid based technique: Detection of dengue virus RNA by PCR can confirm diagnosis (available in
specialist laboratories)
...
Prothrombin time: Increased
...
A 12-year old girl presented with rash in whole body
...
What would be the
differential diagnosis?
Differential diagnosis of fever with rash:
78
Macular or maculo-papular rash:
1
...
3
...
5
...
7
...
9
...
11
...
2
...
4
...
Meningococcal infection
Viral hemorrhagic fever
Leptospirosis
Septicemia with disseminated intravascular coagulation
...
Urticarial rash:
1
...
3
...
2
...
Chicken pox
Shingles
Herpes simplex infection
Nodular rash:
1
...
Erythematous rash:
1
...
3
...
5
...
2
...
4
...
Syphilis
Trypanosomiasis
Typhus (tick and mite)
Anthrax
Rat bite fever
Q
...
He had fever for last few days
...
Write down the probable viral infections
...
Describe the laboratory diagnosis of any two
...
2
...
4
...
Q
...
His routine
blood examination revealed thrombocytopenia
...
a
...
c
...
State the probable diagnosis
...
Name the two tests for the serodiagnosis of the condition
...
Ans:
a
...
c
...
Dengue fever
Dengue virus
ELISA, ICT
Complications:
• Dengue hemorrhagic fever (DHF)
• Dengue shock syndrome (DSS)
80
Title: Blueprint Virology
Description: This document contains elaborate study materials of the Virology course for both Bachelor and Masters level. It covers both General and Systemic Virology. Total page number: 80. There are questions and answers included in various topics like "Cultivation of viruses; Viral genetics and replication; Oncogenic viruses; Hepatitis viruses; Herpes viruses; Non-oncogenic retroviruses; Slow viral infections" and so on.
Description: This document contains elaborate study materials of the Virology course for both Bachelor and Masters level. It covers both General and Systemic Virology. Total page number: 80. There are questions and answers included in various topics like "Cultivation of viruses; Viral genetics and replication; Oncogenic viruses; Hepatitis viruses; Herpes viruses; Non-oncogenic retroviruses; Slow viral infections" and so on.